Prostate, kidney and bladder cancers (urological malignancies) are the most common cause of death among our Veterans. Therefore, there is an urgent unmet need for the management of these malignancies. To address these issues, the applicant has been working in the field of urological malignancies since 1987. There are three main goals of the applicant's research: 1) To investigate the molecular mechanisms of initiation, progression and metastasis of urological malignancies. 2) To identify molecular biomarkers for diagnosis and prognosis of urological cancers. 3) Treatment of urological cancers using natural compounds. To accomplish these goals, the applicant has received several VA and NIH funded projects in collaboration with VA and Non-VA clinicians and scientists. The applicant has been very productive with 350 scientific publications in peer-reviewed journals and has had a distinguished career for 27 years in the VA system. Throughout his career, he has been at the forefront of research into the molecular mechanisms of urological cancers. His research work is supported by several NIH/VA funded projects and currently, he has one VA Merit Review award and two NIH funded RO1 projects. He has trained more than 50 fellows and most of them are faculty members at various institutions with funded research programs. The applicant has extensively collaborated with VA investigators and non-VA investigators in funded program projects and scientific publications. The applicant was the first one to receive a REAP (Research Enhancement Award Program) on prostate cancer from the Department of Veterans Affairs (PI: Dahiya, 1999-2012). He has trained several scientists in collaboration with VA clinician scientists. Recently, the applicant received a VA program project on the ?Role of genetic biomarkers in clinical assessment of prostate cancer? (PIs: Dahiya, Tanaka, Lau, 10-2012-09-2017) in collaboration with four VA scientists and clinicians. Under this program, his team has investigated whether SNPs, CpG methylation, miRNAs and X-linked genes together can predict which localized prostate cancer patients have a higher risk of developing metastasis and thus require more aggressive interventions. Currently, the applicant has a VA Merit Review award ? Regulation of c-Myc/HIF pathway in the management of kidney cancer? (PI: Dahiya, 10/2011-09/2020) and two NIH RO1 projects UO1CA184966 ?Genetic factors for race related prostate cancer? (PI: Dahiya 07/2015-06/2020) and RO1CA199694 ?Molecular biomarkers for kidney cancer prognosis using non-coding RNAs (PI: Dahiya 06/2016-05/2021) In summary, the applicant's scientific contributions are vitally important to the VA mission. He has made ground breaking discoveries in the field of urological cancers and has also provided significant resources to the scientific community and the VA system. The applicant's laboratory has made several significant contributions to the fields of epigenetics (DNA methylation, histone modification, chromatin remodeling), non-coding RNAs (dsRNA, miRNAs), SNPs of various genes and their roles in diagnosis, prognosis, progression, metastasis and risk assessment and treatment of urological malignancies. These are high priority programs for our VA health care system.